Project abstract Principal neurons (PNs) of the lateral superior olive (LSO) in the brainstem of mammals are a key component in the processing of binaural cues used for sound localization that underlie selective attention. They accomplish this by comparing excitatory synaptic inputs driven by the ipsilateral ear with inhibitory inputs driven by the contralateral ear. It is increasingly appreciated that along with their classical role of interaural intensity difference (IID) coding, LSO PNs also encode interaural time differences (ITDs). These two functional roles, along with the tonotopic organization of the LSO, place different demands on the cellular properties of LSO neurons. My major hypothesis is that there is functional segregation of LSO PNs for IID and ITD coding. This functional segregation may be defined by transmitter released, projection pattern, morphology, dendritic integration functions, or synaptic inputs. This proposal will develop core methodologies to access these cellular features of the LSO. Excitatory LSO PNs are biased to higher frequency regions and largely project contralaterally while inhibitory cells are biased to lower frequencies and project Ipsilaterally. Firing response characteristics associated with phase locking and ITD coding are biased toward lower frequency regions, potentially associating with inhibitory PNs. I will investigate the possibility that ipsilateral projecting inhibitory PNs are better adapted for ITD coding while contralateral projecting excitatory PNs are better adapted for IID coding. This potentially provides a means to segregate this information in upstream centers. Critical for understanding whether inhibitory and excitatory cells have distinct functional roles within the circuit is their relative intrinsic cellular properties. To efficiently investigate this I will develop a transgenic mouse line that will allow me to target excitatory and inhibitory cell types during brain slice physiology experiments. My expectation is that inhibitory/ITD coding cells would have lower input resistances, faster membrane time constants, larger diameter and less complicated dendrites, and phasic firing type, whereas, excitatory/IID coding will be associated with more integrative membrane properties. These experiments will yield foundational insights into the cellular organization of the LSO. Efficacy of propagation of action potentials and synaptic potentials in dendrites is a critical component of integrative functions and synaptic plasticity in neurons which cannot be measured from somatic recordings alone. Recent work has revealed dendritic properties that have adapted for ITD coding. In contrast, almost nothing is known of the electrical properties of LSO dendrites or what aspects of dendritic physiology best support IID coding. I will develop methodologies using multiphoton imaging to make unbiased dual dendritic/somatic patch recordings from LSO neurons which allow for the analysis not only of local responses in the dendrites but also signal transformations with propagation to the soma. Combining this information with our developing understanding of the different coding demands on cells along the tonotopic axis, and potentially between PN types, will yield new insights into the relationship between cellular properties and circuit function.